The cullin7 E3 ubiquitin ligase: a novel player in growth control.
Cullin7 (CUL7) is a molecular scaffold that organizes an E3 ubiquitin ligase containing the F-box protein Fbw8, Skp1 and the ROC1 RING finger protein. Dysregulation of the CUL7 E3 Ligase has been directly linked to hereditary human diseases as cul7 germline mutations were found in patients with autosomal-recessive 3-M and Yakuts short stature syndromes, which are characterized by profound pre- and postnatal growth retardation. In addition, genetic ablation of CUL7 in mice resulted in intrauterine growth retardation and perinatal lethality, underscoring its importance for growth regulation. The recent identification of insulin receptor substrate 1, a critical mediator of insulin and insulin-like growth factor-1 signaling, as the proteolytic target of the CUL7 E3 ligase, provided a molecular link between CUL7 and a well-established growth regulatory pathway. This result, coupled with other studies demonstrating interactions between CUL7 and the p53 tumor suppressor protein, as well as the simian virus 40 large T antigen oncoprotein, further implicated CUL7 as a novel player in growth control and suggested pathomechanistic insights into CUL7-linked growth retardation syndromes.
Sarikas
Antonio
A
Department of Oncological Sciences, The Mount Sinai School of Medicine, New York, New York 10029, USA. antonio.sarikas@mssm.edu
Xu
Xinsong
X
Field
Loren J
LJ
Pan
Zhen-Qiang
ZQ
D000818:Animals; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
C506299:CUL7 protein, human; D044842:Cullin Proteins; D044783:F-Box Proteins; C513332:Fbxw8 protein, mouse; D055504:Insulin Receptor Substrate Proteins; D019938:Cyclin D1; D044767:Ubiquitin-Protein Ligases